Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial

Abstract

Objective: This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the α2 agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder.

Methods: Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or placebo (n = 21) for 12 weeks. The primary aim of this study was to determine the safety and tolerability of GXR in youth with anxiety disorders, which involved the analysis of treatment-emergent adverse events (TEAEs), the emergence of suicidal ideation and behaviors, vital signs, and electrocardiographic/laboratory parameters. Exploratory efficacy measures included dimensional anxiety scales (Pediatric Anxiety Rating Scale [PARS] and Screen for Child Anxiety Related Emotional Disorders [SCARED]), as well as the Clinical Global Impression-Improvement (CGI-I) scale. As this was an exploratory study, no inferential statistical analyses were performed.

Results: GXR was safe and well tolerated. Treatment-related mean ± standard deviation changes in heart rate (GXR: 1.8 ± 12 beats per minute [bpm] decrease; placebo: 0.5 ± 11 bpm decrease), systolic blood pressure (GXR: 2.3 ± 11 mm Hg decrease; placebo: 1.7 ± 11 mm Hg decrease), or diastolic blood pressure (GXR: 1.3 ± 9 mm Hg decrease; placebo: 0.9 ± 7 mm Hg increase) were similar between treatment groups. TEAEs, including headache, somnolence/fatigue, abdominal pain, and dizziness, were consistent with the known safety profile of GXR. No differences were observed between treatment groups for PARS and SCARED scores, although at endpoint, a higher proportion of subjects receiving GXR versus placebo demonstrated CGI-I scores ≤2 (54.2% vs. 31.6%), as rated by the clinician investigator.

Conclusions: GXR was well tolerated in pediatric subjects with GAD, SAD, and/or social anxiety disorder. ClinicalTrials.gov Identifier: NCT01470469.

Keywords: adolescent; generalized anxiety disorder; separation anxiety disorder; social anxiety disorder; social phobia; α2 agonist.

Conflict of interest statement

Dr. Strawn has received research support from Eli Lilly, Edgemont, Shire, Forest Research Laboratories, Lundbeck, the National Institute of Mental Health (NIMH), and Neuronetics. He has received royalties from Springer for the publication of two texts and has received material support from Assurex Health. Dr. Compton has received research support from the NIMH and Shire, and currently serves on the editorial board of the Journal of Consulting and Clinical Psychology, Journal of Child and Adolescent Psychopharmacology, and BMC Psychiatry. Dr. Albano has received research support from the NIMH and currently receives honorarium from the American Psychological Association and royalties from Oxford University Press for editorial positions. Dr. Robertson and Mr. Hamdani are employees of Shire and hold stock and/or stock options at Shire. Dr. Rynn has received research support from Eli Lilly and Shire, as well as from the NIMH and the National Institute of Child Health and Human Development.

Figures

FIG. 1.

Subject flow diagram. GXR, guanfacine extended-release.

FIG. 2.

Anxiety symptoms and improvement during double-blind treatment with GXR. PARS (A) and SCARED child-rated (B) and parent-rated (C) scores decreased over the course of treatment in both GXR-treated and placebo-treated subjects. The number of subjects with a CGI-I score ≤2, which indicates “much improved” or “very much improved,” was numerically larger in GXR-treated subjects compared with healthy subjects throughout the treatment duration (D). Error bars represent standard deviation. CGI-I, Clinical Global Impression–improvement; ET, early termination; GXR, guanfacine extended-release; PARS, Pediatric Anxiety Rating Scale; SCARED, Screen for Child Anxiety Related Emotional Disorders.